Successful IVF in a cisgender female carrier using oocytes retrieved from a transgender man maintained on testosterone

AbstractWe describe both phenotype and pathogenesis in two male siblings with typical retinitis pigmentosa (RP) and the potentially X-linked RP (XLRP) carrier phenotype in their mother. Two affected sons, two unaffected daughters, and their mother underwent detailed ophthalmological assessments including Goldmann perimetry, color vision testing, multimodal imaging and ISCEV-standard electroretinography. Genetic testing consisted of targeted next-generation sequencing (NGS) of known XLRP genes and whole exome sequencing (WES) of known inherited retinal disease genes (RetNet-WES). Variant validation and segregation analysis were performed by Sanger sequencing. The mutational load of the RHO variant in the mother was assessed in DNA from leucocytes, buccal cells and hair follicles using targeted NGS. Both affected sons showed signs of classical RP, while the mother displayed patches of hyperautofluorescence on blue light autofluorescence imaging and regional, intraretinal, spicular pigmentation, reminiscent of a carrier phenotype of XLRP. XLRP testing was negative. RetNet-WES testing revealed RHO variant c.404G > C p.(Arg135Pro) in a mosaic state (21% of the reads) in the mother and in a heterozygous state in both sons. Targeted NGQSS of the RHO variant in different maternal tissues showed a mutation load between 25.06% and 41.72%. We report for the first time that somatic mosaicism of RHO variant c.404G > C p.(Arg135Pro) mimics the phenotype of a female carrier of XLRP, in combination with heterozygosity for the variant in the two affected sons.

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Congestive Heart Failure With Rhabdomyolysis and Acute Renal Failure in a Manifesting Female Carrier of Duchenne Muscular Dystrophy With Duplication of Dystrophin Gene

Journal of Clinical Neuromuscular Disease ◽

10.1097/cnd.0b013e3181adcda7 ◽

2009 ◽

Vol 11 (1) ◽

pp. 49-53 ◽

Cited By ~ 9

Author(s):

Atchara Tunteeratum ◽

Rawiphan Witoonpanich ◽

Suchart Phudhichareonrat ◽

Jakris Eu-ahsunthornwattana ◽

Sarinee Pingsuthiwong ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Renal Failure ◽

Acute Renal Failure ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Dystrophin Gene ◽

Female Carrier

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Generation of human induced pluripotent stem cell (iPSC) line from an unaffected female carrier of mutation in SACSIN gene

Stem Cell Research ◽

10.1016/j.scr.2018.10.016 ◽

2018 ◽

Vol 33 ◽

pp. 166-170 ◽

Cited By ~ 1

Author(s):

Candela Machuca ◽

Angel Vilches ◽

Eleonora Clemente ◽

Samuel Ignacio Pascual-Pascual ◽

Arantxa Bolinches-Amorós ◽

...

Keyword(s):

Stem Cell ◽

Pluripotent Stem Cell ◽

Induced Pluripotent Stem Cell ◽

Female Carrier ◽

Ipsc Line ◽

Induced Pluripotent

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Rare Co-Occurrence of Visual Snow in a Female Carrier With RPGRORF15-Associated Retinal Disorder

Frontiers in Genetics ◽

10.3389/fgene.2021.728085 ◽

2021 ◽

Vol 12 ◽

Author(s):

Aekkachai Tuekprakhon ◽

Aulia Rahmi Pawestri ◽

Ragkit Suvannaboon ◽

Ketwarin Thongyou ◽

Adisak Trinavarat ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Disease Onset ◽

Retinal Dystrophy ◽

Female Carrier ◽

Ophthalmological Examination ◽

Early Disease ◽

Rare Form ◽

Inactivation Pattern ◽

Retinal Disorder ◽

Female Carriers

X-linked retinitis pigmentosa (XLRP), a rare form of retinitis pigmentosa (RP), is predominantly caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. Affected males often present with severe phenotypes and early disease onset. In contrast, female carriers are usually asymptomatic or show stationary phenotypes. Herein, we reported an 8-year-old female carrier, a daughter of a confirmed RP father with RPGR mutation, with an early onset of progressive cone-rod pattern retinal dystrophy. Additionally, the carrier experienced visual snow-like symptom as long as she recalled. Ophthalmological examination showed the reduction of visual acuity and attenuation of photoreceptor functions since the age of 5 years. Further analysis revealed a heterozygous pathogenic variant of the RPGR gene and a random X-inactivation pattern. Although she harboured an identical RPGR variant as the father, there were phenotypic intrafamilial variations. The information on the variety of genotypic and phenotypic presentations in XLRP carriers is essential for further diagnosis, management, and monitoring of these cases, including the design of future gene therapy trials.

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Dyskeratosis Congenita Caused by a 3′ Deletion: Germline and Somatic Mosaicism in a Female Carrier

Blood ◽

10.1182/blood.v94.4.1254 ◽

1999 ◽

Vol 94 (4) ◽

pp. 1254-1260 ◽

Cited By ~ 35

Author(s):

T.J. Vulliamy ◽

S.W. Knight ◽

N.S. Heiss ◽

O.P. Smith ◽

A. Poustka ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Failure ◽

Somatic Mosaicism ◽

Dyskeratosis Congenita ◽

Single Amino Acid ◽

Antisense Strand ◽

Female Carrier ◽

Bone Marrow Failure Syndrome ◽

Somatic Tissues ◽

Rna Biogenesis

Abstract X-linked dyskeratosis congenita (DC) is a bone marrow failure syndrome caused by mutations in the DKC1 gene located at Xq28. By 20 years of age, most affected boys develop bone marrow failure, whereas female carriers show a skewed pattern of X-chromosome inactivation. The gene product, dyskerin, is homologous to a yeast protein involved in ribosomal RNA biogenesis, providing a unique insight into a cause of aplastic anemia. Whereas most causative mutations are single amino acid substitutions, and nonsense or frameshift mutations have not been observed, we present here a case of DC caused by a 2-kb deletion that removes the last exon of the gene. Normal levels of mRNA are produced from the deleted gene, with the transcripts using a cryptic polyadenylation site in the antisense strand of the adjacent MPP1 gene, normally located 1 kb downstream of DKC1 in a tail to tail orientation. The predicted truncated protein lacks a lysine-rich peptide that is less conserved than the rest of the dyskerin molecule and is dispensable in yeast, supporting the contention that it may retain some activity and that null mutations at this locus may be lethal. The affected boy had an unaffected brother with the same haplotype around the DKC1 gene and a sister who was heterozygous for the deletion. We conclude therefore that the mother must be a germline mosaic with respect to this deletion. Investigation of her blood cells and other somatic tissues showed that a small proportion of these cells also carried the deletion, making her a somatic mosaic and indicating that the deletion took place early in development.

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Macrophage activation syndrome/haemophagocytic lymphohistiocytosis secondary to Burkholderia cepacia complex septicaemia in an elderly female carrier of X-linked chronic granulomatous disease with extreme lyonisation: ‘cepacia syndrome’ revisited

BMJ Case Reports ◽

10.1136/bcr-2019-230434 ◽

2019 ◽

Vol 12 (8) ◽

pp. e230434 ◽

Cited By ~ 2

Author(s):

Nicolás Urriola ◽

Andrew Williams ◽

Karuna Keat

Keyword(s):

Chronic Granulomatous Disease ◽

Burkholderia Cepacia ◽

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Burkholderia Cepacia Complex ◽

Female Carrier ◽

Granulomatous Disease ◽

Haemophagocytic Lymphohistiocytosis ◽

Stimulating Factor ◽

Activation Syndrome

X-linked carriers of chronic granulomatous disease (CGD) may become phenotypically affected if substantial skewing from lyonisation occurs. We describe a 73-year-old female carrier with an overt CGD phenotype due to skewed lyonisation, complicated by macrophage activation syndrome (MAS)/haemophagocytic lymphohistiocytosis (HLH) secondary to Burkholderiacepacia complex septicaemia that was successfully treated with a combination of three antibiotics, an antifungal, granulocyte colony stimulating factor, intravenous immune globulin (IVIG) and ciclosporin. Fully phenotypic immunodeficiency is possible in X-linked CGD carriers when skewed lyonisation occurs, rendering such patients to all the same sequelae of CGD such as MAS/HLH. MAS/HLH should be thoroughly excluded when evaluating ‘cepacia syndrome’ in non-CGD patients.

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Persistence of skewed X-chromosome inactivation in pre-B acute lymphoblastic leukemia of a female ATRX mutation carrier

Blood Advances ◽

10.1182/bloodadvances.2019000013 ◽

2019 ◽

Vol 3 (17) ◽

pp. 2627-2631

Author(s):

Christian P. Bradley ◽

Cai Chen ◽

Karolyn A. Oetjen ◽

Cheng Yan ◽

Reema Panjwani ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

X Chromosome ◽

Germline Mutation ◽

Mutation Carrier ◽

Lymphoblastic Leukemia ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Female Carrier ◽

Key Points ◽

Skewed X Chromosome Inactivation

Key Points Leukemic blasts of a female carrier of an ATRX germline mutation have persistently skewed inactivation of the X chromosome. Germline mutation in leukemia needs to be interpreted with caution because it is not always pathologic.

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Ischemic Optic Neuropathy in a Female Carrier with Fabry’s Disease

Ophthalmologica ◽

10.1159/000310318 ◽

1992 ◽

Vol 205 (2) ◽

pp. 83-88 ◽

Cited By ~ 21

Author(s):

Haruki Abe ◽

Toyoaki Sakai ◽

Shoichi Sawaguchi ◽

Shigeru Hasegawa ◽

Mineo Takagi ◽

...

Keyword(s):

Optic Neuropathy ◽

Female Carrier ◽

Ischemic Optic Neuropathy ◽

Fabry’S Disease ◽

Fabry's Disease

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Persistent Salmonella Infection in a Female Carrier for Chronic Granulomatous Disease

Annals of Internal Medicine ◽

10.7326/0003-4819-73-4-595 ◽

1970 ◽

Vol 73 (4) ◽

pp. 595 ◽

Cited By ~ 19

Author(s):

ROBERT C. MOELLERING

Keyword(s):

Chronic Granulomatous Disease ◽

Female Carrier ◽

Granulomatous Disease ◽

Salmonella Infection

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Cardiac Involvement in Dystrophin-Deficient Females: Current Understanding and Implications for the Treatment of Dystrophinopathies

Genes ◽

10.3390/genes11070765 ◽

2020 ◽

Vol 11 (7) ◽

pp. 765 ◽

Cited By ~ 1

Author(s):

Kenji Rowel Q. Lim ◽

Narin Sheri ◽

Quynh Nguyen ◽

Toshifumi Yokota

Keyword(s):

Muscular Dystrophy ◽

Molecular Mechanisms ◽

Cardiac Involvement ◽

Gene Mutations ◽

Dystrophin Gene ◽

Becker Muscular Dystrophy ◽

Female Carrier ◽

Daily Life Activities ◽

Cardiac Manifestations ◽

Available Information

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive condition caused primarily by out-of-frame mutations in the dystrophin gene. In males, DMD presents with progressive body-wide muscle deterioration, culminating in death as a result of cardiac or respiratory failure. A milder form of DMD exists, called Becker muscular dystrophy (BMD), which is typically caused by in-frame dystrophin gene mutations. It should be emphasized that DMD and BMD are not exclusive to males, as some female dystrophin mutation carriers do present with similar symptoms, generally at reduced levels of severity. Cardiac involvement in particular is a pressing concern among manifesting females, as it may develop into serious heart failure or could predispose them to certain risks during pregnancy or daily life activities. It is known that about 8% of carriers present with dilated cardiomyopathy, though it may vary from 0% to 16.7%, depending on if the carrier is classified as having DMD or BMD. Understanding the genetic and molecular mechanisms underlying cardiac manifestations in dystrophin-deficient females is therefore of critical importance. In this article, we review available information from the literature on this subject, as well as discuss the implications of female carrier studies on the development of therapies aiming to increase dystrophin levels in the heart.

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